2-Aminothiazole → 4-(Phenylmethyl)-N-2-thiazolyl-1-piperidinepropanamine

To a solution of 4-benzylpiperidine (3.51 g, 20.0 mmol) and DBU (0.030 ml, 0.20 mmol) in THF (40 ml) was dropwise added a solution of acrolein (90%, 1.485 ml, 20.0 mmol) in THF (10 ml) at −20° C. with stirring over a period of 10 minutes. The mixture was stirred for 1 hour while the temperature of the mixture is elevated from −20° C. to −10° C. To the mixture were added 2-amino-1,3-thiazole (2.00 g, 20.0 mmol) and sodium triacetoxyborohydride (8.48 g, 40.0 mmol), successively, at −10° C., and the mixture was stirred for 15 hours while the temperature of the mixture is elevated to room temperature. Under ice cooling, aqueous solution of 1N-sodium hydroxide (120 ml) was added, and the mixture was stirred for 30 minutes and extracted with diethyl ether (60 ml×4). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The concentrate was subjected to column chromatography (silica gel 100 g, ethyl acetate/methanol=1/0 to 85/15), and the desired fraction was concentrated under reduced pressure to give the titled compound (680 mg, 2.16 mmol) as white crystals. Yield 11%.

1. stirringThe mixture was stirred for 1 hour while the temperature of the mixture
2. customis elevated from −20° C. to −10° C
3. stirringsuccessively, at −10° C., and the mixture was stirred for 15 hours while the temperature of the mixture
4. customis elevated to room temperature
5. stirringthe mixture was stirred for 30 minutes
6. extractionextracted with diethyl ether (60 ml×4)
7. dry with materialThe organic layer was dried over magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. concentrationthe desired fraction was concentrated under reduced pressure

ORD record

ord-8124549ede3449a981d8198d86503485

Source dataset

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06562978B1